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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Optogenetic control of cell differentiation in channelrhodopsin-2-expressing OS3, a bipotential glial progenitor cell line
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Optogenetic control of cell differentiation in channelrhodopsin-2-expressing OS3, a bipotential glial progenitor cell line

机译：血管术胶质血管血管胶质细胞系中细胞分化的致敏控制。

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摘要

Alterations in the intracellular ion environment have been identified as one of the signals playing a critical role in the control of cellular proliferation and differentiation; however, the mechanisms responsible for signal transduction remain unclear. Recent studies have reported that channelrhodopsin-2 (ChR2) is a rapidly gated blue light (BL)-sensitive cation channel suitable for the non-invasive control of ion influx. We herein examined the expression of differentiation-associated markers by photo-activation and its signal transduction in ChR2-expressing OS3 (OS3ChR2) cells, which are clonal bipotential glial progenitor cells. Increases were observed in intracellular Na+ and Ca2+ concentrations in OS3ChR2 cells with BL exposure. Alterations in the intracellular ion environment, particularly in Ca2+, led to increases in the expression of oligodendrocyte markers including galactocerebrosides (GalC) and decreases in that of astrocyte markers such as glial fibrillary acidic protein (GFAP). These alterations also triggered activation of the ERK1/2 signaling pathway, which is involved in cell survival, and PI3K/Akt/mTOR signaling pathway, which is involved in oligodendrocyte differentiation, characterized by GalC expression. Moreover, when photo-activated OS3ChR2 cells were injected into mice with lysophosphatidyl choline (LPC)-induced demyelination, deficits in motor function were reduced. Our results demonstrated that signal transduction by ChR2-expressing glial progenitor cells may be controlled through alterations induced in the intracellular ion environment by photo-activation and results in oligodendrOcyte differentiation from glial progenitor cells. Our results also suggest that ChR2-expressing glial progenitor cells have potential as a useful tool for therapeutic approaches to brain and spinal cord disorders associated with oligodendrocyte dysfunctions. (C) 2017 Elsevier Ltd. All rights reserved.
机译：细胞内离子环境中的改变已被鉴定为在控制细胞增殖和分化中发挥着关键作用的信号之一;然而，负责信号转导的机制仍然不清楚。最近的研究报道说，频道流学博止-2（CHR2）是一种适用于离子流入的非侵入性控制的快速门控蓝光（BL） - 敏感阳离子通道。我们在本文中检测了通过光激活的分化相关标记的表达及其在CHR2的OS3（OS3CHR2）细胞中的信号转导，其是克隆双向胶质祖细胞。通过BL暴露在OS3CHR2细胞中的细胞内Na +和Ca2 +浓度中观察到增加。细胞内离子环境中的改变，特别是在Ca2 +中，导致少偶突（Galc）的少突胶质细胞标记物的表达增加，并降低了星形胶质细胞标志物，例如胶质纤维酸性蛋白（GFAP）。这些改变还触发了ERK1 / 2信号传导途径的激活，其参与细胞存活，以及PI3K / AKT / MTOR信号传导途径，其参与寡突胶质细胞分化，其特征在于GA1C表达。此外，当用溶血磷脂酰胆碱（LPC）诱导脱髓鞘将光活化的OS 3CHR2细胞注入小鼠时，减少了电机功能的缺陷。我们的结果表明，CHR2表达的信号转导通过通过光激活在细胞内离子环境中诱导的改变来控制CHR2的胶质祖细胞的转导，并导致寡突祖细胞的少突胶质细胞分化。我们的研究结果还表明CHR2表达的胶质祖细胞具有作为治疗方法的有用工具，用于治疗脑和脊髓紊乱与少突胶质细胞功能障碍相关的脑和脊髓紊乱。 （c）2017 Elsevier Ltd.保留所有权利。

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